Mechanisms responsible for the changes in control of breathing which occur in man during 'long-term' exposure to chronic hypoxia are not well understood. These changes occur at high altitudes in normals and at sea level in patients with various diseases of the heart and lungs; they can lead to pathological consequences due to the exacerbration of arterial hypoxia. If the responsible mechanisms can be elucidated, then more effective and safer treatments may result. The goal of the present research is to gain a better understanding of the regulation of respiration during exposure to hypoxia. The specific aims of this proposal are to directly test, in an animal model, the following hypotheses: 1) the cerebral cortex has an influence on hypoxic control of breathing, 2) the changes in control of breathing occurring after long-term exposure to chronic hypoxia are caused by a diminution in the carotid chemo-reflexive drive to breathe, and 3) polycythemia is a factor in ventilatory control during chronic hypoxia. The first aim will be met by studying respiratory control in chronically maintained cats before and after cortical ablation by sub-pial aspiration under 3 conditions: normoxic recovery (2-4 weeks), short-term hypoxic exposure (3 days) following normoxic recovery, and long-term hypoxic exposure (3-6 weeks) following normoxic recovery. The latter two aims will be met by studying ventilatory control in the awake cat following long-term exposure to chronic hypoxia; we shall determine the effects of 1) carotid body resection and 2) reduction of blood hemoglobin concentration to sea level value. The results will be interpreted by paired t-test, non-linear regression, and analysis of variance techniques such that each animal serves as its own control.